Topical composition for skin treatment to reduce lines and wrinkles of the face and body using a dual dna repair mechanism to address damage caused by aging and ultra-voilet induced damage to the skin with combination of skin turgor enhancement compounds

ABSTRACT

A topical composition for anti-aging and anti-UV damage treatment of the skin includes water soluble extract of  Uncaria  species,  Arabidopsis thaliana  extract, alpha lipoic acid, dimethylethanolamine, tetrahexyldecyl ascorbate, dimethyl sulfoxide,  Glycyrrhiza Glabra  (licorice) root extract, methylsulfonylmethane, phytosterols, D-ribose, tocotrienol, tocopherol, glucosamine hydrochloride,  Pisum sativum  extract; silicates of sodium, magnesium and aluminum, and a dermatologically acceptable liposomal delivery medium. The composition is useful in a method using it for anti-aging skin treatment effecting DNA repair in both the nucleus and the mitochondria. The topical composition can be applied on the skin of a person daily, and can also be applied in a dermal infusion treatment, with or without micro-dermal abrasion or skin suction. Topical application of the composition achieves effective reduction of pigmentation spots, degree of winkles, and improvement of skin color, tone and turgidity, particularly of the eyelid and facial areas.

FIELD OF THE INVENTION

This invention relates to a topical composition for anti-aging skintreatment and a method of anti-aging skin treatment utilizing dualactions of DNA repair in the nucleus and the mitochondria to repairoxidative and non-oxidative DNA damages and a combination of otheringredients that cause the skin to look younger, and remove eyelidbulges and fine lines of the face and body.

BACKGROUND OF THE INVENTION

This application reflects an improvement of the invention of U.S. Pat.No. 8,911,774 of Vincent Giampapa, one of the inventors herein. Suchimprovement provided enhanced suppleness to the skin, anti-agingbenefits and repair of UV-related damage.

Aging is the accumulation of random damage to the building blocks oflife, especially to DNA, certain proteins, carbohydrates and lipids,which begins early in life and eventually exceeds the body's self repaircapabilities.

Photoaging is the complex of damages that accumulate from life-longexposure to solar ultraviolet light (UV-A and UV-B). It produceswrinkling, loss of elasticity, erythema, hyperpigmentation, andincreased risk of skin cancer. UV radiation acts on the epidermisthrough direct exposure, and on the underlying dermis throughcell-to-cell molecular signaling. Collagen fibrils in the extracellularmatrix of the dermis are responsible for the strength and resiliency ofthe skin. Wrinkling occurs due to the loss and scarring of the dermalcollagen fibrils that results from chronic exposure to solar UV.

UV irradiation leads to elevated levels of matrix metalloproteinases inhuman skin (MMPs). One of these enzymes, MMP-1 (also known ascollagenase-1), cleaves collagen type 1, the primary constituent of thecollagen fibrils in the extracellular matrix of the dermis. Theimbalance of MMP-1 promotes the scarring of the collagen fibrilstructures. The resultant disorganization of collagen fibrils in thedermal connective tissue leads to loss of skin tone and wrinkling.

UV-A radiation has been shown to penetrate the under layers of the skin,and produce oxidative DNA damage. Following exposure of the skin toultraviolet radiation free radicals are generated, which frequentlytrigger the release of inflammatory mediators. Among the inflammatorychain activities triggered by free radicals, it is known that thetranscription factors NF-kB and activator protein 1 (AP-1) are activatedby free radicals and pro-inflammatory cytokines, which are generated byfree radical activity.

The UV-induced DNA damage also activates immunosuppressive pathways thatinhibit the cutaneous immune system from reacting to challenges from theenvironment and tumors. The immunosuppressive cytokines TNF-Alpha andIL-10 have been observed among the repertoire of cellular responsesfollowing UV irradiation.

Irradiation by UV-A also acts to damage DNA indirectly, through theformation of oxygen radicals, to oxidize guanine to 8-oxo-guanine innuclear and mitochondrial DNA. The oxidative events of UV-A irradiation,including metabolic stress associated with loss of mitochondrial DNA,also are associated with the inflammatory responses that lead to therelease of collagen-degrading metalloproteinases into the dermal layer.

UV-B radiation, commonly referred to as the sunburn rays, is the onethat cause the most concern. At the molecular lever, it is known thatUV-B irradiation produces non-oxidative DNA damage, which results in DNAstructural changes through dimer formation. More specifically, UV-Birradiation causes DNA damage in skin by linking adjacent bases to formcyclobutane purimidine dimer (CPD). These may be of the thymine-thyminetype, or they may be between adjacent cytosines, or other combinations.CPDs are slowly removed from the DNA by a natural excision repairprocess, which removes about 50% of the CPDs in 24 hours. Furthermore,it is believed that a combination of UV-A and UV-B damages may be theformation of CC-TT dimer tandem doubles. These tandems may occur on thep53 tumor suppressor gene and may lead to the formation of squamous cellcarcinomas. The non-oxidative DNA alteration damage is commonly assessedby quantifying the formation of TT dimers within the cells. By utilizinghuman living epidermal cell equivalents HaCaT Keratinocytes the amountof cyclobutyl pyrimidine TT dimers (CPD) formed can be measured.

As can be appreciated, danger occurs when DNA is damaged but notseverely enough to stimulate apoptosis (natural cell death), the damagedcells then reproduce the unrepaired DNA, which initiates a continuum.The skin loses moisture and becomes dull, dry, and rough without toneand texture. Blotches, hyperpigmentation, fine lines and wrinklesdevelop and, then, premalignant actinic keratoses form. Finally theseage spots may become malignant squamous cell carcinomas.

Various pharmaceutical or cosmetic products have been developed fortreating age spots resulted from chronic UV light exposure. Mostproducts treat age spots by bleaching, and topical color reduction bychemical reactions, however, they do not repair DNA damages, or preventre-occurrence of skin pigmentation. On the other hand, many skin careproducts now include antioxidants to reduce free radicals and addressoxidative damages.

Recently, Arabidopsis thaliana extract containing active component ofoxoguanine glycosylase-1 has been used with liposome for restoring theDNA damaged by oxidative stress in the nucleus and in the mitochondria.However, the function of oxoguanine glycosylase-1 does not addressnon-oxidative DNA damages caused by UV-B.

U.S. Patent Application Publication No. 20050226825 A1 discloses atopical composition containing water soluble extract of Uncaria speciesfor repairing DNA damages caused by UV-B radiation by reducing dimerformation.

As can be appreciated, existing topical skin care products have limitedfunctions in preventing and repairing DNA damages, therefore, havelimited effects in preventing and restoring age related deterioration ofskin conditions, particularly damage of skin about the eyes,

Therefore, it is desirable to have a topical composition that addressesmultiple major causes of skin aging, particularly, photoaging caused byboth oxidative and non-oxidative DNA damages, and inflammatory responsecaused by oxidative stress.

SUMMARY OF THE INVENTION

In one embodiment, the present invention is directed to a topicalcomposition for anti-aging skin treatment. The topical compositionincludes water soluble extract of Uncaria species, Arabidopsis thalianaextract, lipoic acid, dimethylethanolamine, tetrahexyldecyl ascorbate,dimethyl sulfoxide, Glycyrrhiza Glabra (licorice) root extract,methylsulfonylmethane, phytosterols, d-ribose, tocotrienol, tocopherol,glucosamine hydrochloride, Pisum sativum extract, silicates of sodium,magnesium and aluminum, and acetyl hexapeptide 8 within adermatologically acceptable liposomal delivery medium. To thiscomposition may be added Bambusa vulgaris extract which is a form ofbamboo silica.

In another embodiment, the present invention is directed a method ofanti-aging skin treatment that comprises topically applying the topicalcomposition on one or more areas of the skin of a person, which resultsin reduction of pigmentation spots and degree of winkles, andimprovement of skin color tone. The topical composition can be topicallyapplied on the areas of interest one or more times daily. Moreover, thetopical composition can also be applied by dermal infusion treatment.

In a further embodiment, the instant invention is directed to acomposition providing increased turgidity and suppleness to the skin.

Further advantages of the invention will become apparent from thefollowing description showing exemplary embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1, 3 and 5 are photographs of three subjects before use of theinventive composition.

FIGS. 2, 4 and 6 are photographs of the same subjects after about twomonths of use of the composition.

DETAILED DESCRIPTION OF THE INVENTION

In one embodiment, the present invention provides a topical compositionfor anti-aging skin treatment using dual DNA repair mechanism. Thetopical composition comprises a plurality of active components withdifferent functionalities, including antioxidants, DNA repaircomponents, anti-glycation components, anti-inflammatory components,cellular hydration components, age spot reduction components, andcollagen stimulating components in a dermatological acceptable liposomaldelivery medium.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one having ordinaryskills in the art to which the invention pertains.

It should also be understood that various chemicals used herein may havemore than one type of properties described herein. Therefore they may belisted or described in more than one of the categories of the activecomponents. For example, tocopherol acetate is a strong antioxidant, andit also increases collagen synthesis, as such, it is also a collagenstimulating component.

Antioxidants inhibit free radical productions. Decrease in free radicallevels promotes repairing of damaged cell membranes as well as cellularhormonal receptors. Antioxidants also help to inhibit AP-1, which is thekey compound noted to be involved in skin aging and collagen breakdown.Research has shown that lower DNA damage levels also correlate withlower free radical levels. The examples of suitable antioxidantsinclude, but are not limited to, alpha lipoic acid, tocotrienol,tocopherol, tetrahexyldecyl ascorbate, dimethyl sulfoxide, and retinylpalmitate.

Alpha lipoic acid is an extremely potent anti-oxidant that is both waterand fat-soluble. Alpha lipoic acid is used in the topical composition ina concentration range from about 1% to about 5% by weight (w/w).

Tetrahexyldecyl ascorbate is a stable, oil soluble form of Vitamin C. Itis very soluble in ethanol, hydrocarbons, esters and vegetable oils. Ithas been found that tetrahexyldecyl ascorbate penetrates the skin fourtimes better than magnesium ascorbyl phosphate, delivers pure Vitamin Cfifty times better than ascorbic acid. It has been reported thattetrahexyldecyl ascorbate inhibits MMP-2 and MMP-9 over three timesbetter than ascorbic acid, decreases 8-OHdG induced by UV-A radiation,decreases p53 expression induced by UV-B radiation, and increasescollagen synthesis at least twice as much as ascorbic acid. It has alsobeen reported that at a concentration of 0.1% tetrahexyldecyl ascorbatereduces melanin synthesis by 80%. It is believed that tetrahexyldecylascorbate protects the cells against UV-B radiation better than otheresters of Vitamin C. On the other hand, in Korea tetrahexyldecylascorbate is approved as a functional ingredient for whitening at 2%.Therefore, as can be appreciated, tetrahexyldecyl ascorbate is amulti-functional component. It is effective in anti-oxidation, collagensynthesis and protection, whitening, MMP inhibition, and DNA protection.The concentration of tetrahexyldecyl ascorbate in the topicalcomposition is in a range from about 0.5% to about 2% (w/w).

Retinyl palmitate, or vitamin A palmitate, is a common vitaminsupplement for oral administration, and it has also been used in skincare products. Retinyl palmitate is used as an antioxidant. After itsabsorption into the skin, retinyl palmitate is converted to retinol, andultimately to retinoic acid (the active form of Vitamin A).

Dimethyl sulfoxide (DMSO) is a potent anti-oxidant and ananti-inflammatory agent. Dimethyl sulfoxide dissolves both polar andnonpolar compounds and is miscible in a wide range of organic solventsas well as water. More importantly, it has a distinctive property ofpenetrating the skin very readily, and it has the ability to carry othersubstances through membranes. Therefore, in addition to its antioxidantand anti-inflammatory properties, dimethyl sulfoxide is also used as adelivery agent in the instant topical composition. The concentration ofdimethyl sulfoxide is in a range from about 0.5% to about 2% (w/w).

As an important feature of the present invention, the topicalcomposition comprises DNA repair components of natural ingredients. Twodistinct compounds, namely water soluble extract of Uncaria species andArabidopsis thaliana extract, are utilized to repair both mitochondrialand nuclear DNAs.

The Uncaria species herein includes tomentosa, guianensis, pteropoda,homomalla, perrottetii, or rhynchopylla. Preferably, Uncaria tomentosais used in the topical composition. Water soluble extract of an Uncariaspecies can be obtained using hot water, cold water or alcoholextraction of the Uncaria species using methods known in the art. Hotwater extraction of Uncaria species has been known and used for hundredsof years as a natural herbal treatment. Native Indians preparetreatments of Uncaria by drinking hot water extracts as a tea. Recently,U.S. Pat. Nos. 6,361,805, 6,238,675, 6,039,949, and 6,964,784, which arehereby incorporated by reference in their entirety, each teach aparticular hot water extraction method. The method produces a hot waterextract from the bark of Uncaria tomentosa, where the fraction of theextract having a molecular weight less than 10,000 is separated as theextract product. This product is in a form of beige to brown-orangehygroscopic fine powder, and it contains no less than 16% of carboxyalkyl esters and it is readily soluble in water (solubility inwater >400 mg/ml). The water soluble extract of an Uncaria species iscommercially available from various sources, for example, from PhoenixLab. Inc. (Hicksville, N.Y.) and Raintree Nutrition, Inc. (Carson City,Nev.).

NF-kB is known to control the nuclear events that salvage cells fromapoptotic cell death and pro-inflammatory cytokine production (Beg, etal., An essential role for NF-kB in preventing TNF-.alpha. induced celldeath Science 274: 782-784, 1996; Wang et al., TNF-.alpha. and CancerTherapy-induced Apoptosis: Potentiation by Inhibition of NF-KB. Science274: 784-787, 1996). It has been reported that the water soluble extractof the Uncaria species effectively induces apoptosis in HL-60 leukemiccells in vitro, as a result of NF-kB inhibition, hence, it possessesanti-tumor, anti-inflammatory and immune stimulating properties.Moreover, it has been reported that the water soluble extract of theUncaria species enhances DNA repair in both rats and humans, wherein theDNA repair process removes DNA damages in the nucleus, which inhibitscell replication and immune function (see U.S. Pat. No. 6,039,949).Water soluble extract of the Uncaria species has been used orally as asupplement for inhibiting inflammatory response and treating disordersassociated with inflammatory response by inhibiting TNF-.alpha.production or induce apoptosis of white blood cells.

Most recently, as disclosed in U.S. Patent Application Publication No.20050226825 A1, which is hereby incorporated by reference in itsentirety, it has been found in-vitro study that after UV-B exposure,human HaCaT (keratinocyte line) cells incubated with a solution of watersoluble extract of the Uncaria species have substantially lesscyclobutane purimidine dimer (CPD) formation in the nucleus incomparison to untreated cells. Therefore, the water soluble extract ofthe Uncaria species improves skin cell's resistance to DNA damage andenhances DNA repair capacity by reducing formation of CPDs.

Water soluble extract of the Uncaria species is used in the topicalcomposition of the present invention for repairing non-oxidative DNAdamages by reducing CPD formation, and as an anti-inflammatory agentutilizing its NF-kB and TNF-.alpha. inhibition properties. It has beenfound that when water soluble extract of Uncaria tomentosa is used, itsconcentration in the topical composition can be in a range from about0.5% to about 5% (w/w), preferably from about 0.75% to about 3% (w/w).

On the other hand, oxidative stress damages the membrane of cells andthe DNA of the nucleus and mitochondria. Oxidation happens with normalmetabolism and UV-A radiation. It has been reported that 10,000 basesper cell are damaged every day. Oxidative DNA damages cause formation of8-oxo-guanine in mitochondria and an increase in MMP-1 release.Mitochondria have about 1-2% of the total DNA. However, this circularDNA is important because mitochondrial DNA codes for sub-units of ATPsynthase, NADH dehydrogenase, cytochrome oxidase, and other proteins.

Traditionally, oxidative damages are addressed by using antioxidants inskin care products. It is important to understand that antioxidants canonly protect DNA by reducing free radical formation, however,antioxidants cannot repair DNA after it has been excessively damaged.

Oxoguanine glycosylase-1 (OGG1) is a DNA repair enzyme that excises8-oxo-guanine (8 oG). This enzyme has 424 amino acids and a molecularweight of 47 kD in its precursor form in humans. It has been reportedthat oxoguanine glycosylase-1 excises the damaged base and acts with anassociated lyase activity for chain cleavage. Oxoguanine glycosylase-1can be trapped by mitochondrial membranes, and increased levels ofoxoguanine glycosylase-1 are found in the mitochondria of aged livers,indicating that the import of oxoguanine glycosylase-1 needed for DNArepair in mitochondria declines with age.

Oxoguanine glycosylase-1 is found in the plant Arabidopsis thaliana. Theextract of Arabidopsis thaliana is commercially available. It has beenfound that oxoguanine glycosylase-1 encapsulated in liposome canpenetrate mitochondria and repairs mitochondrial DNA effectively.Commercially, oxoguanine glycosylase-1 in liposome is provided by AGIDermatics, (Freeport, N.Y.) under the trade name of Roxisomes™. It hasbeen reported that in-vitro study treatment of keratinocytes with 0.5%Roxisomes™ reduces the amount of damage to the mitochondria fromperoxide by approximately 30% and also prevents further damage overtime.

In one embodiment, Arabidopsis thaliana extract is used in the topicalcomposition for restoring the DNA damaged by oxidative stress in themitochondria and in the nucleus. The concentration of Arabidopsisthaliana extract is in a range from about 0.5% to about 2% (w/w).

As can be appreciated, the unique combination of water soluble extractof the Uncaria species and Arabidopsis thaliana extract in the topicalcomposition of the present invention provides dual actions of DNArepair. The former mainly repairs DNA in the nucleus and the lattermainly repairs DNA in the mitochondria, hence the dual actions of thetopical composition are also referred to as a dual DNA repair mechanism.Furthermore, the dual DNA repair actions address DNA damages caused byboth oxidative and non-oxidative damages. Moreover, theanti-inflammatory property of the water soluble extract of the Uncariaspecies further broadens the spectrum of the protective actions.Therefore, this synergetic and unique combination provides strongadvantages over existing anti-aging skin care technologies, whichtypically focus on only one aspect of the causes, or one type ofrepairing actions. Furthermore, the topical composition of the presentinvention addresses DNA damages caused by both intrinsic (metabolic andnatural aging) and extrinsic (UV radiations) reasons. As can beappreciated, enhancing DNA repair in both the nucleus and themitochondria ultimately reduces CPD formation, which reduces the causeof skin cancer.

In addition to the components enabling DNA repair, the topic compositionfurther comprises D-ribose as an essential material for the DNArepairing process. D-ribose is a pentose present in all livingorganisms. It is an essential element of the structure of the ATPmolecule, and is directly involved in ATP synthesis. It has also beenreported that D-ribose in a cosmetic composition improves cellularrespiration and intracellular ATP production, and it improves metabolismof the cutaneous cells and tissues. The concentration of D-ribose is ina range from about 0.01% to about 0.05% (w/w).

In a further combination with several potent antioxidants describedabove, the topical composition of the present invention effectivelyreduces DNA damages by reducing the cause of oxidative damage, and byeffectively repairing the DNA as damage occurs.

As described above, the water soluble extract of the Uncaria species isan anti-inflammatory agent. Alpha lipoic acid is also a stronganti-inflammatory agent. These compounds inhibit NF-KB and TNF-.alpha.,which are pro-inflammatory compounds activated by UV-A and UV-Bsunlight. The inhibition of NF-KB and TNF-.alpha. in skin cells helps tokeep collagen and elastin from breaking down, caused by metaloproteaseand collagenases.

It is known that glycation of collagen increases uniformly with age,leading to a uniform increase in the glycation-product content of theskin, which accelerates skin wrinkle formation. These glycation productsinclude, for example, pyrraline, carboxymethyl-lysine, pentosidine,crosslines, Ne-(2-carboxyethyl)lysine (CEL), glyoxal-lysine dimer(GOLD), methylglyoxal-lysine dimer (MOLD), 3DG-ARG imidazolone,versperlysines A, B, C, threosidine or, alternatively, advancedglycosylation end products (AGEs).

Anti-glycation components are used in the topical composition to reduceglycation of collagen. Vitamin E is known to significantly reducesglycation and production of AGEs. Tocopherol is a series of organiccompounds consisting of various methylated phenols, which is a class ofchemical compounds of which many have vitamin E activity. Tocotrienols,with four d-isomers, also belong to the vitamin E family. Tocotrienolhas been shown clinically to be 40-50 times stronger and more effectiveat repairing skin damage than regular Vitamin E. Tocopherols andtocotrienols are fat-soluble antioxidants, they can disperse in a cellmembrane, therefore, eliminate free radicals far more efficiently thanregular Vitamin E.

Tocotrienol/tocopherol complex is commercially available under the tradename of Tocomin® from CAROTECH Inc. (Edison, N.J.). Tocomin® is a seriesof products contain natural occurring mixture of tocotrienols andtocopherol extracted and concentrated from virgin crude palm oil/palmfruits (Elaeis guineensis). The Tocomin® also contain otherphytonutrients such as plant squalene, phytosterols, co-enzyme Q10 andmixed carotenoids that are naturally extracted together withtocotrienols from palm fruits. Tocotrienol/tocopherol complex is used inthe topical composition of the present invention in a concentrationrange from about 0.05% to about 0.2% (w/w) of Tocomin® (50% c).

Examples of suitable collagen stimulating components include, but arenot limited to, methylsulfonylmethane, phytosterols, tetrahexyldecylascorbate, metallic sicates, Pisum sativum (pea) extract, anddimethylethanolamine, and estrogen.

Methylsulfonylmethane (MSM) is an organic source of bioavailable sulfur,which is crucial to body function and structure, found naturally in thebody and in all living organisms. Methylsulfonylmethane inhibits crosslinking of collagen and therefore is useful to reduce hardening ofconnective tissue with age. Methylsulfonylmethane has also been used inophthalmic formulations as a skin permeation enhancer facilitatingpermeation of the formulation through the skin, when the formulation isapplied to the eyelids. In addition, methylsulfonylmethane is requiredin DNA repair. Methylsulfonylmethane is used in the topical compositionat a concentration in a range from about 0.1% to about 0.5% (w/w).

Phytosterols used in the topical composition are derived from vegetableoils. Naturally occurring phytosterols are usually a mixture of varioussterols (e.g., campesterol, stigmasterol, among others). Structurallysimilar to cholesterol, phytosterols have been found to protect skinsweakened by hormonal deficiencies, re-densify the dermis to remodel theskin, and smooth out structural wrinkles. The skin treated byphytosterols is visibly firmer and younger, and the depth of structuralwrinkles visibly diminishes. Furthermore, it is believed that the activecomponents of naturally occurring phytosterols retard inflammationprocesses.

Furthermore, a second different combination may be used, namely, acomplex of silicates of sodium, magnesium and aluminum; Pisum sativum(pea) extract; and glucosamine hydrochloride is used in the topicalcomposition for increasing the production of collagen, elastin andhyaluronic acid, and induces cell proliferation and differentiation.Such silicates are known sources of silica. Also, bamboo silica has beenused in skin care products as a cross-linking agent, providing strengthand resilience to collagen and elastin connective tissues. Pisum sativum(pea) extract has been found containing phenolic compounds, such asbenzoic and cinnamic acids, cinnamic acid derivatives, flavone andflavonol glycoside, and to possess antioxidant properties. Glucosamineis an amino sugar and a prominent precursor in the biochemical synthesisof glycosylated proteins and lipids. Glucosamine hydrochloride is usedfor simulating hyaluronic acid production.

A complex of bamboo silica extract, Pisum sativum extract andglucosamine hydrochloride is commercially available under the trade nameof Dermox SRC from Barnet Products Corporation (Englewood Cliffs, N.J.).An increased production of collagen, elastin and hyaluronic acid makesskin firmer and makes deeper wrinkles less visible. The concentration ofDermox SRC in the topical composition is in a range from about 0.5% toabout 2% (w/w).

It is to be appreciated that silicates of sodium, magnesium and aluminummay be used in addition to or in lieu of bamboo silica, also known asBambusa vulgura. Where said metallic silicates are used, it alsodesirable to include acetyl hexapeptide-8 and phenoxyethonal and,optionally, ethylhexylglycerin for enhanced suppleness of the skin andreduction of wrinkles.

Estrogen has been known to stimulate both collagen and hyaluronic acidfor some time. Estrogens are a group of steroid compounds that functionas the primary female sex hormone in human body. The three naturallyoccurring estrogens are estradiol, estriol and estrone. Phytoestrogensare a group of naturally occurring nonsteroidal plant compounds. Becauseof their structural similarity with estradiol (17-.beta.-estradiol),phytoestrogens have the ability to cause estrogenic effects. Suitableestrogens for the purpose of the present invention include, but are notlimited to, estriol, estradiol, estrone, phytoestrogens, or combinationthereof. In one embodiment, estriol is used for stimulating collagen orelastin production.

It is known that most of the hydration in the skin is dependent onhyaluronic acid levels in the intra and extra-cellular matrix. The morehyaluronic acid the skin contains, the more water the skin will retain.Hyaluronic acid production normally decreases with age, consequently,both the cells and the gel substance between the cells becomes lesshydrated. This reduces delivery of nutrients necessary for skinregeneration and DNA repair into the cells, as well as reduces cellwaste removal out of the cell. Therefore, poor metabolic pathwayfunction can be caused by poor cell nutrition due to poor cellhydration. This leads to rapid and premature cellular aging. Cellularhydration compounds increase hyaluronic acid production. Enhancingcellular hydration provides softer looking and feeling skin, and helpsto reduce wrinkle depth and new wrinkle formation.

Dimethylethanolamine is used in the topical composition as a cellularhydration compound. Dimethylethanolamine is a nutrient naturallyproduced in the human brain. When applied on the skin,dimethylethanolamine gives an almost immediate increase in theappearance of tone and continues to firm skin over time.Dimethylethanolamine is also an antioxidant. Dimethylethanolamine isconsidered as a food-grade substance, safe to use in dermatologicalproducts. In the topical composition of the present invention,dimethylethanolamine is in a concentration range from about 0.2% toabout 0.8% (w/w).

Age spot reduction components are used to treat and inhibit agedependent color changes to the skin. These compounds decrease pigmentdepositions and help to even skin tone. Furthermore, in terms ofpigmentation, previously described DNA repair components continuouslyreduce, as well as inhibit, the formation of new age relatedpigmentations which are also known as lipofuscin deposits.

Glycyrrhiza Glabra (licorice) root extract is used in the topicalcomposition of the present invention as an age spot reduction component,in a concentration range from about 0.005% to about 0.03% (w/w).Glycyrrhiza Glabra (licorice) root extract contains active component ofglabridin. Glabridin has a strong tyrosinase-inhibition activity, whichis 25 times higher than Kojic acid and 75 times higher than ascorbicacid. Glabridin is also an antioxidant and has UV absorbing property.

Glycyrrhiza Glabra (licorice) root extract is commercially availableunder the trade name of Licorice P-TH from Barnet Products Corporation(Englewood Cliffs, N.J.). In vivo study has shown that at aconcentration of 0.05% of Licorice P-TH, the extract effectivelydecreases post-inflammatory hyperpigmentation in more than 80% of theindividuals tested. In the topical composition of the present invention,Glycyrrhiza Glabra (licorice) root extract is used in a concentrationrange from about 0.005% to about 0.03% (w/w).

Additionally, the water soluble extract of the Uncaria species describedabove is also believed to function as a bleaching agent.

In one embodiment, the topical composition comprises water solubleextract of Uncaria species, Arabidopsis thaliana extract, lipoic acid,dimethylethanolamine, tetrahexyldecyl ascorbate, dimethyl sulfoxide,Glycyrrhiza Glabra (licorice) root extract, methylsulfonylmethane,phytosterols, d-ribose, tocopherol, Pisum sativum extract, glucosaminehydrochloride, and a dermatological acceptable liposomal deliverymedium.

As described above, one major feature of the topical composition of thepresent invention is its dual actions in DNA repair in both the nucleusand the mitochondria. To achieve an effective DNA repair in the nucleusand in the mitochondria, the active components need to be deliveredthrough the cellular membrane to the target areas. To accomplish this, aliposomal delivery system or medium is used in the topical compositionto encapsulate the active components and to enhance their penetrationthrough the epidermis and then to enter the dermis layer. Liposomes canpenetrate through cellular membrane and deliver the active components tothe inside of cells. Other delivery vehicles, such as nosome orrivosome, can also be used in the topical composition.

The medium further comprises solvents, emulsifiers, emollients, binders,and moisturizers known in the art. In one exemplary embodiment, themedium of the topical composition comprises water, butylene glycol,propylene glycol, glyceryl stearate, PEG-100 stearate, brassiccacampestris/aleurites fordi oil copolymer, cyclopentasiloxane anddimethicone/vinyl dimethlcone crosspolymer, cyclopentasiloxane, C12-15alkyl octonoate, cetyl alcohol, bis-diglyceryl polyacyladipate-2,lecithin, maltodextrin, sorbitan stearate, ethylene/acrylic acidcopolymer, titanium dioxide, methyl glucose sesquistearate, PEG-20methyl glucose sesquistearate, acrylates/C10-30 alkyl acrylatecrosspolymer, sodium silicate, magnesium aluminum silicate, acetylhexapeptide-8, polyoxyethanol, and butyrospermum parkii (shea butter).

The topical composition may further comprise one or more preservatives,such as phenoxyethanol, methylparaben, ethylparaben, butylparaben,triethanolamine, and tetrasodium EDTA. These chemicals haveantimicrobial activities for preserving the product. The concentrationof the preservatives is sufficient to inhibit microbial growth, withoutcausing skin irritation or interference of the active componentsdescribed above. Optionally, the topical composition may also comprise afragrance and coloring agents such as Yellow 5 and Red 40.

The topical composition of the present invention can be provided in avariety of forms such as lotion, cream, spray, gel, and aqueoussuspension.

In a further aspect, the present invention provides a method ofanti-aging skin treatment. In one embodiment, the method comprisestopically applying an effective amount of the topical composition of thepresent invention on one or more areas of the skin of a person. The areamay include, but not limited to, forehead, eye area, perioral area,cheek, the entire face, neck, chest or hands. In one embodiment, thetopical composition is topically applied on the areas one or more timesdaily. Typically, the skin area is covered by a thin layer of thetopical composition.

In one study among 59 women between age 30 and 60, after applying thecream set forth herein once daily in the night for a period of from onemonth to twelve months, more than 80% of the subjects achievednoticeable improvements in reduction of the degree of wrinkles, and morethan 85% of the subjects achieved noticeable improvements in the skincolor tone. The improvements were observed in the forehead, crows feetand eye area, perioral area, and the face in general. A quantitativeevaluation of the pigmentation spots on the face of the subjects usingDigital Visia Complexion Analysis showed an average reduction of thefeature count of the spots from 33.15% to 56.25% upon completion of thetreatment.

Shown in FIGS. 1, 3 and 5 are photographs of the eye area of three ofthe above subjects prior to treatment with the inventive composition.FIGS. 2, 4, and 6 show changes in appearance of the same three subjectsafter two months of use. As may be seen, the results of the therapy aremost noticeable.

In another study, the topical composition was used in a skin infusion ordermal infusion treatment. Dermal infusion is a procedure that providesnoninvasive exfoliation and delivers a topical solution under pressureto treat dermatological conditions. It has been used to treat rosacea,dehydration, acne, and post-inflammatory hyperpigmentation. In oneembodiment, the topical composition of the present invention, in theform of an aqueous suspension, can be filled into a known dermalinfusion device and then applied to the skin. The topical compositionmay be applied with or without micro-dermal abrasion or skin suction, aswell as applied topically to the skin in a separate dual compartmentsyringe applicator where the different mixtures of the dual DNA repaircompound and the skin tightening compound are kept separated until theyexit the applicator device and mixed together at the time of use.

All publications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety.

While the invention has been disclosed in connection with certainpreferred embodiments, this should not be taken as a limitation to allof the provided details. Modifications and variations of the describedembodiments may be made without departing from the spirit and scope ofthe invention, and other embodiments should be understood to beencompassed in the present disclosure as would be understood by those ofordinary skill in the art.

We claim:
 1. A method of reducing pigmentation spots, treating wrinklesand improving skin color tone of skin in a person in need thereofcomprising topically applying to one or more areas of the skin, aneffective amount of a composition comprising as active agents: (a)arabidopsis thaliana extract in a concentration range from about 0.5% toabout 2% (w/w); (b) a water soluble extract of Uncaria species in aconcentration range from about 0.5% to about 5% (w/w); (c) alpha lipoicacid in a concentration range from about 1% to about 5% (w/w); (d)dimethylethanolamine in a concentration range from about 0.2 to about0.8% (w/w); (e) tetrahexyldecyl ascorbate in a concentration range fromabout 0.5% to about 2% (w/w); (f) dimethyl sulfoxide in a concentrationrange from about 0.5% to about 2% (w/w); (g) glycyrrhiza glabra(licorice) root extract in a concentration range from about 0.005% toabout 0.3% (w/w); (h) methylsulfonylmethane in a concentration rangefrom about 0.1 to about 0.5% (w/w); (i) phytosterols in a concentrationrange from about 0.1 to about 0.6% (w/w); (j) D-ribose in aconcentration range from about 0.01 to about 0.05% (w/w); (k) a mixtureof tocopherol and phytonutrients in an a concentration range of fromabout 0.5% to about 2% (w/w), wherein the phytonutrients are plantsqualene, phyotsterols, co-enzyme Q10 and mixed carotenoids; (l) acomplex of silicates of sodium, magnesium and aluminum, Pisum sativumextract and glucosamine hydrochloride in an amount of from about 1.0% toabout 10% (w/w); (m) a medium for delivering liposomes; and (n)preservatives; and wherein the composition provides DNA repair of thenucleus and mitrocondria.
 2. The method of claim 1, in which saidcomplex including silicates comprising: sodium silicate and magnesiumaluminum silicate.
 3. The method of claim 2, further comprising: acetylhexapeptide-8.
 4. The method of claim 3, further including:phenoxyethanol and ethylhexylglycerin.
 5. The method of claim 3, furthercomprising: Bambusa vulgris extract.
 6. The method of claim 5, whereinsaid topical composition is topically applied to the one or more areasof skin one or more times daily.
 7. The method of claim 5, wherein saidtopical composition further comprises estriol.
 8. The method of claim 5,wherein the one or more areas of skin are on the forehead, eye area,perioral area, cheek, face, neck, chest or hands, or body.
 9. The methodof claim 7, wherein said topical composition is topically applied on theone or more areas of skin with dermal infusion.
 10. The method of claim9, wherein the dermal infusion is micro-dermal abrasion or skin suction.